Schlicht, Erik M.

AbstractBackground and AimPrimary sclerosing cholangitis (PSC) typically develops in middle‐age adults. Little is known about phenotypic differences when PSC is diagnosed at various ages. Therefore, we sought to compare the clinical characteristics of a large PSC cohort based on the age when PSC was diagnosed.MethodsWe performed a multicenter retrospective review to compare the features of PSC among those diagnosed between 1–19 (n = 95), 20–59 (n = 662), and 60–79 years (n = 102).ResultsThose with an early diagnosis (ED) of PSC were more likely to have small‐duct PSC (13%) than those with a middle‐age diagnosis (MD) (5%) and late diagnosis (LD) groups (2%), P < 0.01, and appeared to have a decrease risk of hepatobiliary malignancies: ED versus MD: hazard ratio (HR), 0.25; 95% confidence interval (CI) 0.06–1.03, and ED versus LD: HR, 0.07; 95% CI 0.01–0.62. Cholangiocarcinoma was diagnosed in 78 subjects (ED n = 0, MD n = 66, and LD n = 12) and was more likely to be diagnosed within a year after the PSC diagnosis among those found to have PSC late in life: ED 0% (0/95), MD 2% (14/662), and LD 6% (6/102), P = 0.02. Similarly, hepatic decompensation was more common among those with LD‐PSC versus younger individuals: LD versus MD: HR, 1.64; 95% CI 0.98–2.70, and LD versus ED: HR, 2.26; 95% CI 1.02–5.05.ConclusionsThose diagnosed with PSC early in life are more likely to have small‐duct PSC and less likely to have disease‐related complications. Clinicians should be vigilant for underlying cholangiocarcinoma among those with PSC diagnosed late in life.

AbstractBackground & AimsPrimary biliary cirrhosis (PBC) is characterized by chronic cholestasis and disease‐specific antimitochondrial antibodies (AMA). A high prevalence of AMAs in first‐degree relatives (FDRs) of PBC probands has been reported, although the natural history of such patients has not been described. We aimed to assess the risk of developing PBC in AMA+ FDRs of patients with PBC.MethodsFirst‐degree relatives recruited to the Mayo Clinic PBC Genetic Epidemiology Registry and Biorepository were followed for disease onset after recruitment. Development of PBC was ascertained via self‐report during a telephone interview and/or via proband report on a questionnaire. Chi‐squared test and t‐test were used to assess the differences between categorical and continuous variables respectively. A mixed‐effects model was used to assess the change in biochemical profiles over time.ResultsForty AMA+ and 423 AMA− subjects were included and followed for a median of 8.9 and 8.4 years respectively. Overall, 3% (n = 15) of FDRs were diagnosed with PBC, and AMA+ FDRs had a higher risk than AMA− FDRs (24% vs. 0.7%, P < 0.01). However, among undiagnosed FDRs, only 4% of AMA+ (n = 1) and 0.4% of AMA− (n = 1) FDRs were diagnosed with PBC (P = 0.17) during the follow‐up period. None of the AMA+ FDRs with normal alkaline phosphatase at baseline developed PBC in follow‐up.ConclusionsOur results suggest a low risk of developing PBC over time in FDRs of patients with PBC, particularly those without biochemical evidence of cholestasis at baseline. These data are useful in counselling and reassuring relatives of their overall favourable prognosis.

SummaryBackgroundThe relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown.AimTo validate associations reported in previous studies and to identify novel environmental exposures among PSC patients.MethodsWe performed a multicenter, case–control analysis utilising self‐administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259).ResultsSmoking was associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4–0.7) but not among those PSC patients without IBD (OR, 0.9; 95% CI 0.7–1.2). Compared to controls, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT; OR, 0.5; 95% CI 0.4–0.7) and were more likely to have recurrent urinary tract infections (OR, 1.6; 95% CI 1.2–2.3). PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3–0.6) and grilled/barbecued meat (OR, 0.8; 95% CI 0.7–0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well done (OR, 1.3; 95% CI 1.2–1.5).ConclusionsIBD (rather than PSC) is associated with smoking. Women with PSC are more likely to have recurrent urinary tract infections and less likely to receive HRT. Dietary intake and methods of food preparation differ in PSC patients when compared to controls.